Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

Olfactomedin 4 通过 Negativ 抑制前列腺癌细胞的生长和转移

• 批准号: 10929107
• 负责人: GRIFFIN RODGERS
• 金额: $ 64.05万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10929107
• 关键词: 13q12; 13q14; 14q; Adult; American; Anterior; BRCA2 gene; Bioinformatics; Biological; Biological Process; C57BL/6 Mouse; CD44 gene; Cadherins; Cancer Cell Growth; Cancer Etiology; Cathepsins; Cell Adhesion; Cell Proliferation; Cell Separation; Cell physiology; Cell surface; Cells; Cessation of life; Chromosomes; Colon Carcinoma; Colonic Neoplasms; Development; Diagnosis; E-Cadherin; Ectopic Expression; Epithelial Cells; Epithelium; Evaluation; Exons; FOXO1A gene; Family; Family member; Gene Expression Regulation; Genes; Genitourinary system; Goals; Homeostasis; Human; Human Genome; In Vitro; Inflammation; Invaded; Lectin; Loss of Heterozygosity; Malignant neoplasm of prostate; Messenger RNA; Metadata; Metastatic Neoplasm to the Bone; Modeling; Molecular; Mus; Natural Immunity; Neoplasm Metastasis; OLFM4 gene; Organoids; Prognosis; Prostate; Prostatic Epithelium; Prostatic Neoplasms; Proteins; RB1 gene; Reporter; Reporting; Retinoblastoma; Seminal fluid; Serum; Signal Pathway; Solid Neoplasm; Stomach Neoplasms; Stromal Cell-Derived Factor 1; Susceptibility Gene; Tissues; Tube; Tumor Suppressor Genes; Tumor Suppressor Proteins; Up-Regulation; Urethra; Xenobiotic Metabolism; advanced prostate cancer; cancer type; cell preparation; forkhead protein; improved; in vivo; male; malignant breast neoplasm; malignant stomach neoplasm; men; migration; novel; olfactomedin; postnatal development; prostate cancer cell; prostate cancer progression; single-cell RNA sequencing; 13q12; 13q14; 14q; Adult; American; Anterior; BRCA2 gene; Bioinformatics; Biological; Biological Process; C57BL/6 Mouse; CD44 gene; Cadherins; Cancer Cell Growth; Cancer Etiology; Cathepsins; Cell Adhesion; Cell Proliferation; Cell Separation; Cell physiology; Cell surface; Cells; Cessation of life; Chromosomes; Colon Carcinoma; Colonic Neoplasms; Development; Diagnosis; E-Cadherin; Ectopic Expression; Epithelial Cells; Epithelium; Evaluation; Exons; FOXO1A gene; Family; Family member; Gene Expression Regulation; Genes; Genitourinary system; Goals; Homeostasis; Human; Human Genome; In Vitro; Inflammation; Invaded; Lectin; Loss of Heterozygosity; Malignant neoplasm of prostate; Messenger RNA; Metadata; Metastatic Neoplasm to the Bone; Modeling; Molecular; Mus; Natural Immunity; Neoplasm Metastasis; OLFM4 gene; Organoids; Prognosis; Prostate; Prostatic Epithelium; Prostatic Neoplasms; Proteins; RB1 gene; Reporter; Reporting; Retinoblastoma; Seminal fluid; Serum; Signal Pathway; Solid Neoplasm; Stomach Neoplasms; Stromal Cell-Derived Factor 1; Susceptibility Gene; Tissues; Tube; Tumor Suppressor Genes; Tumor Suppressor Proteins; Up-Regulation; Urethra; Xenobiotic Metabolism; advanced prostate cancer; cancer type; cell preparation; forkhead protein; improved; in vivo; male; malignant breast neoplasm; malignant stomach neoplasm; men; migration; novel; olfactomedin; postnatal development; prostate cancer cell; prostate cancer progression; single-cell RNA sequencing

Olfactomedin4 (Olfm4) is expressed in normal mouse prostate. However, Olfm4+ cells in the murine prostate have not been well characterized. In this study, we generated an Olfm4eGFP reporter mouse line with C57BL/6 mice and investigated the distribution of Olfm4/eGFP-expressing cells during postnatal development from P1, P7, P14, P20, P42, P56 to adult male mouse prostate and urethral tube. We observed Olfm4/eGFP expression in urogenital and prostatic epithelial cells during early postnatal development, which persisted into adulthood in urethral-tube and anterior-prostate (AP) epithelium. We found Olfm4+ cells are E-cadherin+/CD44+/Foxa1+ and some of subpopulation are Ck8+/Ck5+/Sca-1-/Ck4-/Syn- in the adult mouse AP epithelium. Functional studies of single-cell preparations of Olfm4/eGFP-expressing cells isolated from adult Olfm4eGFP mouse prostate demonstrated that Olfm4+ cells can grow and form colonies, spheres, or organoids in culture. Bioinformatic analysis of Olfm4+ cells using single-cell RNA sequencing meta data in adult mouse urethra (GSE145865) identified upregulation of genes related to cell and tissue migration and development, as well as upregulation of xenobiotic metabolism signaling pathways. In conclusion, Olfm4eGFP mouse is a novel model to further study Olfm4's biological functions and Olfm4+ cells may contribute importantly to cellular processes supporting development and homeostasis of the epithelium in murine prostate and urethral tube.

Olfactomedin4（OLFM4）在正常小鼠前列腺中表达。但是，鼠前列腺中的OLFM4+细胞尚未得到很好的表征。在这项研究中，我们用C57BL/6小鼠生成了一个OLFM4EGFP记者小鼠系列，并研究了从P1，P1，P7，P7，P14，P20，P42，P42，P56，P56，P56，成年雄性小鼠前列腺和尿素管的产后发育过程中OLFM4/EGFP表达细胞的分布。我们观察到产后早期发育期间泌尿生殖器和前列腺上皮细胞中的OLFM4/EGFP表达，在尿道管和前后（AP）上皮中持续存在成年。我们发现OLFM4+细胞是E-钙粘蛋白+/CD44+/FOXA1+，其中一些亚群是成年小鼠AP上皮中的CK8+/CK5+/SCA-1-/CK4-/SYN-。从成年OLFM4EGFP小鼠前列腺中分离出的OLFM4/EGFP表达细胞的单细胞制剂的功能研究表明，OLFM4+细胞可以在培养中生长并形成菌落，球形或类动物。使用单细胞RNA测序元数据对成年小鼠尿道（GSE145865）中的单细胞RNA测序元数据对OLFM4+细胞进行生物信息学分析，确定了与细胞和组织迁移和发育相关的基因上调，以及脑型生物生物代谢信号传导途径的上调。总之，OLFM4EGFP小鼠是一种新型模型，旨在进一步研究OLFM4的生物学功能，OLFM4+细胞可能对支持鼠前列腺和尿道管中上皮的发育和稳态的细胞过程重要贡献。